NST-6179 for Liver Disease

Recruiting at 14 trial locations

Overseen By Michelle Yokley

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: NorthSea Therapeutics B.V.

Must be taking: Parenteral nutrition

Disqualifiers: Cirrhosis, Hepatic impairment, Low BMI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NST-6179 (also known as SEFA-6179 or Orziloben) for individuals with liver disease linked to long-term parenteral nutrition, where nutrition is given intravenously. The trial aims to assess the safety and effectiveness of this treatment in managing liver problems. It is divided into two parts, each testing different doses of NST-6179 against a placebo. Individuals with intestinal failure-associated liver disease (IFALD) for at least six months and who are on intravenous nutrition might be suitable candidates for this study. As a Phase 2 trial, it focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that NST-6179 is likely to be safe for humans?

Research has shown that NST-6179, also known as Orziloben, has been tested for safety in both healthy individuals and those with liver issues due to intestinal failure. Earlier studies with healthy volunteers found the drug to be generally well-tolerated, with no major safety concerns.

These studies examined the drug's effects on the body and its processing within the body. Results have been promising regarding safety. However, research continues, and more information will emerge as further studies are conducted. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver disease?

Researchers are excited about NST-6179 for liver disease because it offers a fresh approach compared to current treatments like antivirals, steroids, or liver transplants. Unlike these options, NST-6179 is designed to target liver disease at a molecular level, potentially addressing the root causes rather than just alleviating symptoms. With doses of 800 mg and 1200 mg being tested, the treatment could provide a more effective and less invasive alternative, offering hope for improved patient outcomes and quality of life.

What evidence suggests that NST-6179 might be an effective treatment for liver disease?

Research has shown that NST-6179 may benefit liver health. In healthy individuals, a similar treatment lowered liver enzymes like AST and ALT, which indicate liver damage. Animal studies suggest that NST-6179 can prevent liver issues such as fat buildup, bile duct problems, and scarring. Specifically, in preterm piglets with liver disease, this treatment stopped liver damage and reduced swelling and scarring. These findings suggest that NST-6179 could help protect the liver in individuals with liver conditions related to intestinal failure. Participants in this trial will receive either 800 mg or 1200 mg of NST-6179, or a matched placebo, to further evaluate its effects on liver health. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Adults over 18 with Intestinal Failure-Associated Liver Disease (IFALD) who have been on parenteral nutrition for at least 6 months can join. They must have certain liver enzyme levels above normal or high bilirubin, but not too high, and meet other blood test criteria.

Inclusion Criteria

Your platelet count is at least 120,000 per cubic millimeter.

My total bilirubin level is 2.0 mg/dL or less, and I don't have Gilbert's Syndrome.

Your blood clotting time should be normal if you are not taking any blood-thinning medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive 800 mg of NST-6179 or placebo once daily for 4 weeks

4 weeks

Daily administration

Treatment Part B

Participants receive 1200 mg of NST-6179 or placebo once daily for 12 weeks

12 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NST-6179

Trial Overview The trial is testing NST-6179's safety and effects in two parts: Part A gives a daily oral dose of either the drug or placebo for four weeks; Part B may increase the dose for twelve weeks based on earlier results.

How Is the Trial Designed?

Group I: Part B- 1200mg NST-6179 Experimental Treatment 1 Intervention

up to 12 subjects

Group II: Part B matched NST-6179 placebo Experimental Treatment 1 Intervention

up to 6 subjects

Group III: Part A-800 mg NST-6179 Experimental Treatment 1 Intervention

up to 12 subjects

Group IV: Part A matched NST-6179 placebo Experimental Treatment 1 Intervention

up to 6 subjects

NST-6179 is already approved in United States for the following indications:

Approved in United States as SEFA-6179 for:

• Intestinal Failure-Associated Liver Disease (IFALD)

Who Is Running the Clinical Trial?

NorthSea Therapeutics B.V.

Lead Sponsor

Trials

7

Recruited

590+

Published Research Related to This Trial

In a study of three obese patients with biopsy-confirmed nonalcoholic steatohepatitis, treatment with the weight reduction medication orlistat for 6-12 months resulted in significant weight loss (22-42 lb) and notable clinical and histopathological improvements.

This suggests that orlistat may be a promising option for managing nonalcoholic steatohepatitis in obese patients, especially given the limited treatment options currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orlistat in the treatment of NASH: a case series. Harrison, SA., Ramrakhiani, S., Brunt, EM., et al.[2018]

Orlistat was found to improve several biochemical markers of liver function in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), including reductions in alanine aminotransferase and aspartate aminotransferase levels, based on a meta-analysis of 330 patients from various trials.

Despite these improvements, orlistat did not significantly affect liver fibrosis scores and showed no notable benefits in patients specifically diagnosed with NASH, indicating it may be more suitable as a supplementary treatment for NAFLD rather than a primary therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of orlistat in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Wang, H., Wang, L., Cheng, Y., et al.[2020]

In a study of 52 patients with nonalcoholic fatty liver disease (NAFLD), orlistat treatment for 6 months led to a significant reduction in serum alanine transaminase (ALT) levels and improved liver steatosis as seen on ultrasound, indicating its efficacy beyond just weight loss.

While orlistat was associated with a higher degree of fibrosis and increased serum glucose and insulin levels, it still demonstrated a beneficial effect on liver health in NAFLD patients, suggesting careful monitoring is needed during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Zelber-Sagi, S., Kessler, A., Brazowsky, E., et al.[2021]

In a long-term study of 101 patients with nonalcoholic steatohepatitis (NASH), the combination of ursodeoxycholic acid (UDCA) and vitamin E significantly improved liver function tests, with 80% of patients normalizing their AST levels.

The treatment was well tolerated, with only a 5% withdrawal rate due to side effects, indicating it is a safe option for managing NASH over an extended period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: long-term results. Pietu, F., Guillaud, O., Walter, T., et al.[2014]

In a study of 14 obese patients with nonalcoholic steatohepatitis (NASH), treatment with orlistat for 6 months led to a significant reduction in liver fat in 70% of patients, with some achieving normal liver fat content.

Orlistat also improved liver inflammation and fibrosis, with 35% of patients returning to normal inflammatory activity and 71% showing some degree of improvement in fibrosis, indicating its potential as a therapeutic option for NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). Hussein, O., Grosovski, M., Schlesinger, S., et al.[2018]

Citations

1. northseatherapeutics.com northseatherapeutics.com/en/programs/orziloben/

Orziloben Even healthy subjects receiving 1,000 mg once-daily for 14 days showed reductions from baseline in AST, ALT and GGT liver enzymes, and bilirubin.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10527514/

A medium chain fatty acid analogue prevents intestinal failure ... SEFA-6179 prevented liver steatosis, prevented bile duct proliferation, and reduced the Ishak fibrosis stage. Secondary outcomes included histologic biomarkers ...

3. forbion.com forbion.com/news-insights/news/northsea-therapeutics-initiates-phase-2a-trial-of-orziloben-nst-6179-in-intestinal-failure-associated-liver-disease-ifald/

NorthSea Therapeutics Initiates Phase 2A Trial Preclinical studies have demonstrated the efficacy of Orziloben in preventing severe cholestasis, fibrosis, and other key markers of liver ...

4. northseatherapeutics.com northseatherapeutics.com/server/multimediaserve/93/Orziloben-LPS-induced-inflammation.pdf?hash=2aa9646f8640e159f4405c4cf3564b4dd19f91fd8f660c927dd3fa1dccc37234

A medium-chain fatty acid analogue prevents endotoxin ... We sought to investigate whether SEFA-6179 would be protective against liver injury in a murine model of PN-associated hepatosteatosis and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0016508523008089

A Medium-Chain Fatty Acid Analogue Prevents Intestinal ... In a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis and reduced bile duct proliferation and fibrosis.

6. northseatherapeutics.com northseatherapeutics.com/en/news/northsea_therapeutics_initiates_phase_2a_trial_of_orziloben_nst_6179_in_intestinal_failure_associated_liver_disease_ifald/

NorthSea Therapeutics Initiates Phase 2A Trial of ... Phase 2a study evaluating the safety, tolerability, PK, and PD of Orziloben ... (NST-6179) in Intestinal Failure-Associated Liver Disease (IFALD). 22 February ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05181085

NCT05181085 | Study of NST-6179 in Healthy Subjects A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

8. mountsinai.org mountsinai.org/clinical-trials/study-of-nst-6179-in-adult-subjects-with-intestinal-failure-associated-liver-disease-ifald

A Study of NST-6179 in Subjects With Intestinal Failure- ... Summary: This is a phase 2a, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), ...

9. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-orziloben-nst-6179-for-patients-with-intestinal-failure-associated-liver-disease/

Study on the Safety and Effects of Orziloben (NST-6179) for ... This study investigates the safety and effects of Orziloben (NST-6179) in treating patients suffering from Intestinal Failure-Associated ...